Unusual conjunctival melanocytic proliferations. Report of five cases and review of the literature.

Indeterminate melanocytic proliferations of the conjunctiva have both benign and malignant features that previously made these lesions nearly impossible to categorize in existing classification schemes. With the evolution of immunohistochemistry and molecular genetics, however, subclassifications have emerged that allow for a more tailored diagnosis and management. These conjunctival melanocytic proliferations include deep penetrating nevus, granular cell nevus, and nevoid melanoma. There remains a small subset of conjunctival melanocytic proliferations that defy precise characterization as nevi, primary acquired melanosis, or melanomas despite currently available ancillary diagnostic modalities and remain indeterminate. We highlight these unusual types of nevi and melanomas, with an update on their morphologic, immunohistochemical, and molecular genetic characteristics.

CHOROIDAL OSTEOMA IN AN INFANT.

PURPOSE: To describe a case of choroidal osteoma with macular involvement in an infant that was treated with transpupillary thermotherapy. METHODS: A case report. RESULTS: An 11-month-old infant presented for retinopathy of prematurity follow up examination and was found to have a three disc-diameter round, orange, subretinal, slightly elevated lesion with well-defined margins in the superior macula of the left eye. B-scan ultrasonography showed a slightly elevated, highly reflective choroidal mass with acoustic shadowing. A diagnosis of choroidal osteoma was made. Six months later, repeat examination under anesthesia (EUA) showed the lesion to be increasing in size and encroaching on the fovea. Given demonstrated growth and the risk of central vision loss, the patient was treated with transpupillary thermotherapy (TTT). Subsequent EUAs, over a period of four months, have shown complete decalcification with no subsequent growth. CONCLUSION: Choroidal osteomas are benign lesions that can be sight threatening if located in the macula. TTT in this case resulted in complete regression of a sight threatening extrafoveal choroidal osteoma at four month follow up.

Intraosseous hemangioma of the orbit: a case report involving pre-operative embolization with reconstruction using a custom porous polyethylene implant.

A 28-year-old female presented with a slowly enlarging, left cheek mass over two years. She underwent neuroimaging and was found to have a well-defined, low attenuating lesion with thickened vertical trabeculation of the left zygoma, consistent with intraosseous hemangioma. To minimize the risk of severe intraoperative hemorrhage, the patient underwent embolization of the mass by neuro-interventional radiology two days prior to resection. The patient subsequently underwent a left anterior orbitotomy and partial zygoma resection followed by reconstruction of the lateral orbit with a custom porous polyethylene zygomaxillary implant. The postoperative course was uneventful with a good cosmetic outcome.

Pediatric Orbital Roof Fractures: A Ratio of Orbital Dimensions Correlated to Prevalence of Fracture.

Objective Orbital roof fractures are more likely to occur in younger children, specifically younger than 7 years. Cranium to face ratio decreases with age; however, there is no definition for measurement of the neurocranium or face. We propose using the length of the orbital roof as a measurement of the neurocranium and length of the orbital floor as a tool to estimate midface size. The purpose of this study is to test this measurement as a correlation rate of orbital roof fractures within the pediatric population. Design This is a retrospective study. Setting This study was done at the LeBonheur Children's Hospital. Participants Sixty-six patients with orbital roof fractures were identified and stratified by gender and age, specifically younger than 7 years and 7 years or older. Main Outcome Measures The main outcome measures were orbital roof length, floor length, and ratio thereof. Results Mean orbital roof length was 43.4 ± 3.06 and 45.1 ± 3.94 mm for patients <7 and ≥7 years, respectively ( p = 0.02). Mean orbital floor length was 41.3 ± 2.99 and 47.7 ± 4.19 for patients <7 and ≥7 years, respectively ( p < 0.00001). The mean roof to floor ratio (RTFR) for patients <7 years was 1.051 ± 0.039 and for patients ≥ 7 years was 0.947 ± 0.031 ( p < 0.00001). Conclusion As children age, the relative length of the orbital roof decreases when compared with the orbital floor. The RTFR was more than 1.0 in children younger than 7 years. These differences were statistically significant when compared with children 7 years and older. This measurement shift follows the differences noted in orbital fracture patterns during childhood.

Effect of Premature Tube Extrusion for Simple Congenital Nasolacrimal Duct Obstruction: A Comparison of Monocanalicular and Bicanalicular Intubation.

ABSTRACT: The objective of this article is to compare the incidence of premature dislocation of silicone tubes and the effect on treatment success between monocanalicular (MCI) and bicanalicular (BCI) intubation in pediatric patients with simple congenital nasolacrimal duct obstruction. Retrospective comparative case series of 108 eyes of 78 pediatric patients with simple congenital nasolacrimal duct obstruction who underwent probing with either BCI (n = 38 eyes) or MCI (n = 70 eyes) from 2017 to 2020. Premature tube extrusion was defined as any tube removed prior to the 3 month postoperative appointment. Success was defined as resolution of tearing 3 months post tube removal. Ages ranged from 10 months to 5.35 years (mean, 1.95 years; Standard deviation (SD), 0.91). Premature tube extrusion occurred in 15 eyes with BCI and 29 eyes with MCI. Success rates were not significantly different regardless of intubation type between the planned tube removal (90.6%) and the premature tube extrusion cohorts (84.1%), P = 0.89. There was no significant difference in treatment success between the planned tube removal (92.7% MCI, 87% BCI) and the premature tube extrusion cohorts (86.2% MCI, 80% BCI). Complications included 2 infections (1 MCI, 1 BCI) and 2 cases of tube related keratopathy (1 MCI, 1 BCI) that all resolved with tube removal. There were 2 BCI patients that presented to the emergency department for premature tube extrusion. Silicone intubation regardless of stent type is an effective treatment for simple congenital nasolacrimal duct obstruction. There was no significant difference in treatment success between tubes that extrude prematurely, and tubes removed at term based on type of intubation.

Effect of Age at Primary Intraocular Lens Implantation on Refractive Growth in Young Children.

PURPOSE: To evaluate the effect of age at primary intraocular lens (IOL) implantation on rate of refractive growth (RRG3) during childhood. METHODS: A retrospective chart review was performed for children undergoing primary IOL implantation during cataract surgery. RRG3 was calculated for one eye from each patient using the first postoperative refraction, last refraction that remained stable (< 1.00 diopters [D] change/2 years), and the corresponding ages. RRG3 values for pseudophakic patients operated on from ages 0 to 5 months were compared with values for patients operated on at ages 6 to 23 months and 24 to 72 months. Patients with refractive errors that stabilized were grouped by age at surgery to compare age at refractive plateau. RESULTS: Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria. There was a statistically significant difference in RRG3 among age groups. The mean RRG3 value was -19.82 ± 5.23 D for the 0 to 5 months group, -22.32 ± 7.45 D for the 6 to 23 months group (0 to 5 months vs 6 to 23 months, P = .43), and -9.64 ± 11.95 D for the 24 to 72 months group (0 to 5 months vs 24 to 72 months, P = .01). CONCLUSIONS: Age at primary IOL implantation affects the RRG3, especially for children 0 to 23 months old at surgery. Surgeons performing primary IOL implantation in infants may want to use age-adjusted assumptions, because faster refractive growth rates can be expected in young children. [J Pediatr Ophthalmol Strabismus. 2020;57(4):264-270.].

Indirect, Non-Thermal Atmospheric Plasma Promotes Bacterial Killing in vitro and Wound Disinfection in vivo Using Monogenic and Polygenic Models of Type 2 Diabetes (Without Adverse Metabolic Complications).

A novel atmospheric plasma device that uses indirect, non-thermal plasma generated from room air is being studied for its effects on wound disinfection in animal wounds of monogenic and polygenic murine models of type 2 diabetes. As a proof-of-concept report, the goal of this study was to demonstrate the efficacy and safety of the indirect non-thermal plasma (INTP) device in disinfecting polycarbonate filters established with Pseudomonas aeruginosa (PAO1) biofilms as well as wound disinfection in diabetic murine wounds. Dorsal excisional wounds in BALB/c, polygenic TALLYHO, and monogenic db/db mice established with PAO1 infection all demonstrated a 3-log colony-forming unit (CFU) reduction when subjected to a course of 20-min INTP treatments. Importantly, blood glucose and body weights in these animals were not significantly impacted by plasma treatment over the study period. Plasma safety was also analyzed via complete blood count and comprehensive metabolic panels, showing no deleterious systemic effects after 3 consecutive days of 20-min plasma applications. Therefore, the results obtained demonstrated the Pseudomonas aeruginosa isolates were highly sensitive to INTP in vitro, CFU reduction of infectious Pseudomonas in wounds of diabetic mice after INTP treatment is far superior to that of non-treated infected wounds, and the application of INTP shows no indication of toxic effects. Our results are consistent with indirect non-thermal atmospheric plasma as a promising adjunct to disinfecting wounds.

Exogenous polyunsaturated fatty acids (PUFAs) alter phospholipid composition, membrane permeability, biofilm formation and motility in Acinetobacter baumannii.

Acinetobacter baumannii is a ubiquitous multidrug-resistant bacteria that is found on a variety of surfaces, including skin, hair and soil. During the past decade, A. baumannii has emerged as a significant cause of nosocomial infections in the United States. Recent studies have highlighted the ability of some bacteria to utilize a wide variety of fatty acids as a membrane remodelling strategy. Considering this, we hypothesized that fatty acids may have an effect on the emerging pathogen A. baumannii. Thin-layer chromatography indicated structural alterations to major phospholipids. Liquid chromatography/mass spectrometry confirmed the assimilation of numerous exogenous polyunsaturated fatty acids (PUFAs) into the phospholipid species of A. baumannii. The incorporation of fatty acids affected several bacterial phenotypes, including membrane permeability, biofilm formation, surface motility and antimicrobial peptide resistance.

db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet.

To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass.

Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.

Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+ cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease.

Pancreatic ß-Cell production of CXCR3 ligands precedes diabetes onset.

Type 1 diabetes mellitus (T1DM) results from immune cell-mediated reductions in function and mass of the insulin-producing ß-cells within the pancreatic islets. While the initial trigger(s) that initiates the autoimmune process is unknown, there is a leukocytic infiltration that precedes islet ß-cell death and dysfunction. Herein, we demonstrate that genes encoding the chemokines CXCL9, 10, and 11 are primary response genes in pancreatic ß-cells and are also elevated as part of the inflammatory response in mouse, rat, and human islets. We further established that STAT1 participates in the transcriptional control of these genes in response to the pro-inflammatory cytokines IL-1ß and IFN-γ. STAT1 is phosphorylated within five minutes after ß-cell exposure to IFN-γ, with subsequent occupancy at proximal and distal response elements within the Cxcl9 and Cxcl11 gene promoters. This increase in STAT1 binding is coupled to the rapid appearance of chemokine transcript. Moreover, circulating levels of chemokines that activate CXCR3 are elevated in non-obese diabetic (NOD) mice, consistent with clinical findings in human diabetes. We also report herein that mice with genetic deletion of CXCR3 (receptor for ligands CXCL9, 10, and 11) exhibit a delay in diabetes development after being injected with multiple low doses of streptozotocin. Therefore, we conclude that production of CXCL9, 10, and 11 from islet ß-cells controls leukocyte migration and activity into pancreatic tissue, which ultimately influences islet ß-cell mass and function. © 2016 BioFactors, 42(6):703-715, 2016.